Several factors are changing the landscape of cervical cancer control, including a better understanding of the natural history of HPV, promising new screening approaches using HPV DNA testing, and the recent licensure of the first prophylactic HPV vaccine targeting the two most common high-risk types of HPV, 16 and 18. We propose to refine our Cervical Cancer Screening Model to be capable of assessing the costs, benefits, and cost-effectiveness of primary prevention (vaccination), secondary prevention (screening), and strategies that combine both. Our specific aims are: (1) to refine a natural history model to function as an open population- based simulation model capable of forecasting incidence, mortality, and costs associated with different cervical cancer control strategies. This model will be calibrated to the United States population using the best available data, including observed patterns in HPV type-specific prevalence, invasive cancer, and temporal variation in factors such as sexual behavior and smoking;(2) to develop a dynamic transmission model of HPV 16 and 18 to estimate the population-level impact of a type-specific vaccination taking into account biological and host factors, vaccine properties, behavioral issues, and herd immunity. We will assess the incremental benefit of vaccinating boys in addition to girls under different scenarios;compare the costs and benefits of policies restricting vaccination to young girls not yet sexually active with policies extending vaccination to women in their late 20s;explore how uncertain assumptions about sexual mixing patterns affect results;and project temporal trends in type-specific HPV prevalence;(3) to assess the cost-effectiveness of alternative cervical cancer prevention strategies for a the general U.S. population as well as for subgroups that differ in their socioeconomic, demographic, and cervical cancer risk profile. We will explore how the cost-effectiveness of a combined screening and vaccination program could change over time, evaluate the effect of vaccination on the test performance of current HPV diagnostics;and assess how vaccine delivery (target age, upper age limit, coverage by age and risk group), vaccine characteristics, and programmatic features influence projected benefits and cost-effectiveness.